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      Markers of cytotoxicity and oxidative DNA damage in Diabesity: A new age illness

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          Abstract

          Background:

          The oral mucous membrane is particularly sensitive to certain types of systemic disorders such as anemia, vitamin deficiencies, infectious diseases, hormonal disturbances and can be objectively reproduced through definite measurements using cytomorphometry.

          Objectives:

          The objective of the study is to evaluate the quantitative and qualitative changes in cytological buccal smears of obese individuals with type II diabetes (Group 1 = 20), obese individuals without type II diabetes (Group 2 = 20), individuals with type II diabetes without obesity (Group 3 = 20) by comparing with controls (individuals without obesity and without type II diabetes) (Group 4 = 20).

          Materials and Methods:

          Buccal mucosal cells were scraped from study participants and were subjected to morphometric analysis (Magnus Pro software). Clinical history, hemoglobin A1c, heights and weights of participants were measured and consequently, their body mass index was calculated. Quantitative parameters (nuclear area, cytoplasmic area, nucleo-cytoplasmic ratio) and qualitative parameters (micronuclei [MN], nuclear budding, nuclear disintegration, apoptosis, necrosis) were assessed among the groups. The data were statistically interpreted using SPSS software version 20.0.

          Results:

          There is an increase in nuclear diameter and nuclear: cytoplasmic ratio of Groups 1 and 3 relative to Group 2. The qualitative assessment revealed MN and nuclear disintegration in Group 1 and 3 individuals. In addition, other qualitative changes such as nuclear budding and apoptotic bodies were evident in patients with type II diabetes.

          Conclusion:

          The aforementioned qualitative and quantitative parameters facilitate early diagnosis and identification of individuals at risk of developing new age systemic illnesses such as diabetes and obesity.

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          Most cited references20

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          Cytokinesis-block micronucleus cytome assay.

          The cytokinesis-block micronucleus cytome assay is a comprehensive system for measuring DNA damage, cytostasis and cytotoxicity. DNA damage events are scored specifically in once-divided binucleated (BN) cells and include (a) micronuclei (MNi), a biomarker of chromosome breakage and/or whole chromosome loss, (b) nucleoplasmic bridges (NPBs), a biomarker of DNA misrepair and/or telomere end-fusions, and (c) nuclear buds (NBUDs), a biomarker of elimination of amplified DNA and/or DNA repair complexes. Cytostatic effects are measured via the proportion of mono-, bi- and multinucleated cells and cytotoxicity via necrotic and/or apoptotic cell ratios. Further information regarding mechanisms leading to MNi, NPBs and NBUDs formation is obtained using centromere and/or telomere probes. The assay is being applied successfully for biomonitoring of in vivo genotoxin exposure, in vitro genotoxicity testing and in diverse research fields such as nutrigenomics and pharmacogenomics as well as a predictor of normal tissue and tumor radiation sensitivity and cancer risk. The procedure can take up to 5 days to complete.
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            Molecular and structural basis of cytokine receptor pleiotropy in the interleukin-4/13 system.

            Interleukin-4 and Interleukin-13 are cytokines critical to the development of T cell-mediated humoral immune responses, which are associated with allergy and asthma, and exert their actions through three different combinations of shared receptors. Here we present the crystal structures of the complete set of type I (IL-4R alpha/gamma(c)/IL-4) and type II (IL-4R alpha/IL-13R alpha1/IL-4, IL-4R alpha/IL-13R alpha1/IL-13) ternary signaling complexes. The type I complex reveals a structural basis for gamma(c)'s ability to recognize six different gamma(c)-cytokines. The two type II complexes utilize an unusual top-mounted Ig-like domain on IL-13R alpha1 for a novel mode of cytokine engagement that contributes to a reversal in the IL-4 versus IL-13 ternary complex assembly sequences, which are mediated through substantially different recognition chemistries. We also show that the type II receptor heterodimer signals with different potencies in response to IL-4 versus IL-13 and suggest that the extracellular cytokine-receptor interactions are modulating intracellular membrane-proximal signaling events.
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              Microvascular recruitment is an early insulin effect that regulates skeletal muscle glucose uptake in vivo.

              Insulin increases glucose disposal into muscle. In addition, in vivo insulin elicits distinct nitric oxide synthase-dependent vascular responses to increase total skeletal muscle blood flow and to recruit muscle capillaries (by relaxing resistance and terminal arterioles, respectively). In the current study, we compared the temporal sequence of vascular and metabolic responses to a 30-min physiological infusion of insulin (3 mU. min(-1). kg(-1), euglycemic clamp) or saline in rat skeletal muscle in vivo. We used contrast-enhanced ultrasound to continuously quantify microvascular volume. Insulin recruited microvasculature within 5-10 min (P < 0.05), and this preceded both activation of insulin-signaling pathways and increases in glucose disposal in muscle, as well as changes in total leg blood flow. Moreover, l-NAME (N(omega)-nitro-l-arginine-methyl ester), a specific inhibitor of nitric oxide synthase, blocked this early microvascular recruitment (P < 0.05) and at least partially inhibited early increases in muscle glucose uptake (P < 0.05). We conclude that insulin rapidly recruits skeletal muscle capillaries in vivo by a nitric oxide-dependent action, and the increase in capillary recruitment may contribute to the subsequent glucose uptake.
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                Author and article information

                Journal
                J Oral Maxillofac Pathol
                J Oral Maxillofac Pathol
                JOMFP
                Journal of Oral and Maxillofacial Pathology : JOMFP
                Wolters Kluwer - Medknow (India )
                0973-029X
                1998-393X
                Oct-Dec 2022
                22 December 2022
                : 26
                : 4
                : 589-590
                Affiliations
                [1 ]Department of Oral Pathology, Microbiology and Forensic Odontology, Dental Institute, RIMS, Ranchi, Jharkhand, India
                [2 ]Department of Oral Pathology and Microbiology, ITS-CDSR, Ghaziabad, Uttar Pradesh, India
                Author notes
                Address for correspondence: Dr. Ankita Tandon, Department of Oral Pathology, Microbiology and Forensic Odontology, Dental Institute, RIMS, Ranchi, Jharkhand, India. E-mail: drankitatandon7@ 123456gmail.com
                Article
                JOMFP-26-589
                10.4103/jomfp.jomfp_132_21
                10112118
                373f22c7-b6cc-4910-a0aa-2cb1041f5095
                Copyright: © 2022 Journal of Oral and Maxillofacial Pathology

                This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

                History
                : 03 May 2021
                : 04 September 2021
                : 05 September 2021
                Categories
                Original Article

                Pathology
                cytomorphometry,diabetes mellitus,obesity
                Pathology
                cytomorphometry, diabetes mellitus, obesity

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